Occasional comments on genetics, genomics and gene expression by Steve Mount. For news and shorter, more timely, posts see "News on Genetics."

Saturday, June 04, 2005

Selection vs. differential allele flow

The media is reporting (NYTimes; Economist) that there is a paper in press in The Journal of Biosocial Science that attributes the pattern of inherited diseases among Ashkenazi Jews to selection for intelligence.This hypothesis breaks not one but several taboos by talking about race, selection and intelligence, so I'm reluctant to say anything at all about it.However, I think that they missed something (I won't be sure until I see the paper, which is not out yet). Selection, "red in tooth and claw," need not be invoked.Differential migration out of the population could have a powerful effect and seems to have been overlooked.In a minority population with asymmetric gene flow (in other words, whenever the rate of assimilation into greater society exceeds the rate of acquisition of new converts) any genetic variation that disfavors assimilation will increase in frequency in the minority population.It is plausible that intelligence could be enhanced by this (for example, if intelligence improved one's ability to learn Torah or become a rabbi and those things made assimilation less likely).It is also plausible that alleles causing non-lethal genetic diseases could actually be favored within a minority population by reducing the probability that affected individuals would leave, which seems likely if the community provided care not available outside and not needed by healthier relatives who were therefore more likely to leave.

7 comments:

Intelligence itself can be an asymmetric force on assimilation. Humans are well known for assortative mating along many potent (skin, language, symmetry, location) criteria and intellgence is certainly one of them. Don't know what the correlation between couple's intelligence is but probably around .4 to .6. These days it must be higher since marriage on the basis of education level is so strong, but even in the past it must have had some effect. Anyway, migration out of jewish groups would have been hindered by higher IQ on the basis of assortative mating, although to make this be disproportionate would take soem strained reasoning about rigidity in upper classes; and a realtinship betwen upper classes and intellignece which may or not be there ... Probably simpler to argue that only someone really dumb would exchange judaism for any of the other moronic religions available in europe.

Now that I have read the actual article, Given the vacuous handwavingof many of the other comments in it, I find this quote particularly unsatisfying.

":Other selective factors have been suggested. “Winnowing through persecution” suggeststhat only the smartest Jews survived persecution. Why this should be so is not clear.There was no similar outcome in other groups such as Gypsies who have faced frequentpersecution (Crowe and Kolsti, 1991)."Surely there are many other differences, including the emphasis on education that might hide IQ effects.

Another inconvenient quote:

":There is scarcely any support in the literaturefor social effects like home environment on IQ (Rowe, 1993). A standard textbook on IQ,after reviewing environmental effects, concludes that “. . . , it is all too easy to throw upone’s hands in despair” (Mackintosh, 1998),"This is just nonsense. IQ can be raised artificially wiht all sorts of training and a good education and educated home life has clear effects on IQ. The author confuses the heritability fo IQ which is confounded by education adn simple measures of IQ wich are directly affected by education.

While this simple error may show a bias in the paper, it doesn't necessarily affect the core reasoning; so it's annoying but not damning.

Another strange quote:"A fair amount of classical commentary on the Jews has beenpreserved, and there is no sign that anyone then had the impression that Jews wereunusually intelligent." -- My impression is that turn of the last century americans didn't think Jews were very smart either - just loathesome. But that is just my impression and as most anecdotal views are, this is just silly basis for scientific discussion.

and on .."The key cultural precondition among the Jews was a pattern of social organization thatrequired literacy, strongly discouraged intermarriage, and that could propagate itself overlong periods of time with little change. Literacy (which does not itself require high intelligence)was probably important in the shift from a nation to an urban occupational caste(Botticini and Eckstein, 2002),..."

IQ measures get most of their power form identifying the least able; and most measures are pretty inadequate sorting average from above average. So literacy is in fact an excellent stadn in for high IQ (to counter the authors' naive commetns ...

"Eventually, as the Ashkenazi population of the Polish-Lithuanian Commonwealth increased,more and more Jews became craftsmen—there are after only so manymanagerial and financial slots. Still, for 800 to 900 years, from roughly 800 AD to 1650or 1700 AD, the great majority of the Ashkenazi Jews had managerial and financial jobs,jobs of high complexity, and were neither farmers nor craftsmen. In this they differedfrom all other settled peoples of which we have knowledge."

While all the discussion about money lending and intelletually demanding jobs is plausible, the scholarship of IQ alluded above is so flawed that this hirotical scholarship also seems suspect. Even so, succesful farming is not a mindless task as the authors seem to imply, but a complex skill that the authors themselves may not find easy. So all this seems like hand waving to me, adn not very convincing.

and on .."On the other hand, there are some indicationsthat poorer families tended to be small ones." Not very convincing!!!

and on .."It is likely that the selective pressures affectingthe medieval Ashkenazi were far stronger and somewhat different, because such a highpercentage had cognitively demanding jobs, and because the Ashkenazi niche was sospecifically demanding of accounting and management skills, while upper classeselsewhere experienced a more diverse set of paths to wealth."This seems to be pushing the argument in much too procrustean a way. Where oh hwere are the carefully weighed alternatives???

"Gene flow from neighboring non-Jewish populations has been low,averaging less than 0.5% per generation (Hammer et al., 2000)."It would be so useful to presetn such a statemetn with some degree of sketpcisim .. how certain is this -- what might a reasonable range be ... what potentially confounding information is there??? This seems like a very cricital componetn of the argument -- and yet it is given such analytic short shrift -- shame on the authors!

further on they say:"From the perspective of a large collection of largely neutral genetic variationAshkenazim are essentially European, not Middle Eastern."Hmm - how does that fit with the low gene flow?

Finally, this seesm to be the meat of the argument and everything else really is window dressing and not very relevant at that:"But that is as expected: genetic diseases made common by drift would be veryunlikely to cluster in only a few metabolic paths, as if on a few pages of a biochemistrytext. The existence of these categories or disease clusters among the Jews suggestsselective forces at work, just as the many different genetic disorders affectinghemoglobin and the red cell in the Old World tropics suggest selection, which we know isfor malaria resistance." So how strong is this argument? - Unfortuantely we are given really very little empricial evidence to support it!!

Finally, a verifiable argument --- "Some believe that the elevated disease frequencies reflect genetic drift (Risch et al.,2003), but drift is an extremely implausible explanation for the pattern. First, there isstrong statistical evidence that the sphingolipid storage mutations are products ofselection. Conservative population-genetic calculations of the probability of a deleteriousmutant achieving an appreciable frequency are negligible (see below). The probabilitythat four such unlikely mutation distributions occurred by chance in genes that haveclosely related functions, that all have a similar biochemical result, is harder to estimatebut must be extraordinarily small: we provide some estimates of this probability below." Unfoertunately, I don't know enough to verify it .. but at least someone should be able to.

Now this looks interesting .. seems like a hypothesis that may merit "further investigation" as they say ...Second and most important,the sphingolipid mutations look like IQ boosters. The key datum is the effect of increasedlevels of the storage compounds. Glucosylceramide, the Gaucher storage compound,promotes axonal growth and branching (Schwartz et al., 1995). In vitro, decreasedglucosylceramide results in stunted neurons with short axons while an increase overnormal levels (caused by chemically inhibiting glucocerebrosidase) increases axon lengthand branching. There is a similar effect in Tay-Sachs (Walkley et al., 2000; Walkley,2003): decreased levels of GM2 ganglioside inhibit dendrite growth, while an increaseover normal levels causes a marked increase in dendritogenesis. This increaseddendritogenesis also occurs in Niemann-Pick type A cells, and in animal models of Tay-Sachs and Niemann-Pick."

Now, this seems really very intersting and even somewhat convincing evidence: "Gaucher patients are clearly a veryhigh IQ subsample of the general population."

I'm beginning to ask myself, How do I get some Glucosylceramide?

OK -- now this does get more and more interesting: Ever since torsion dystonia among the Ashkenazim was first recognized, observers havecommented on the unusual intelligence of patients. Flatau and Sterling (Eldridge, 1976)describe their first patient as showing “an intellectual development far exceeding hisage”, and their second patient as showing “extraordinary mental development for hisage.”

Ah well, there seems to be even more intersting speculation here:Recent work (Evans et al., 2004) supports this hypothesis. Evans et al. show thatmicrocephalin, a gene controlling brain size has evolved rapidly throughout the primatelineage leading to humans and that this evolutionary process exhibits strong signs ofpositive selection (see also Wang and Bing, 2004). Microcephalin and BRCA1 both showsigns of positive selection during primate evolution, share BRCT domains, and havecritical functions in regulating the development of neural stem cells. Evans et al. suggestthat the observed positive selection on BRCA1 has been driven by its effect on braindevelopment rather than tumor suppression. It may be, then, that the Ashkenazi DNArepairmutations in genes such as BRCA1 may be the most recent manifestation of anevolutionary trend that goes back many millions of years, from lemurs to humansubpopulations."

My suspicions about the earlier hand waving is forcing me to be very sceptical about this, but if there is some basis to this, it really is very exciting!

I don't understand the relevance of the argumetn about financiers and genetic pressure -- it seems such a WEAK argument, whereas the actual mutations, if they are intellectually efffective, seeem like a powerful source of real experiment.

Ok -- some good quai-experimental data:"The results are summarized in Table 6. We note that the software picked up most of theclusters we had independently discovered, and several of them (lytic vacuole assembly,sphingolipid metabolism, glycosyl hydrolase activity) have statistical significance farbeyond the 0.01 heuristic for corrected P-values. Furthermore, the DNA-repair cluster weidentified is right on the edge of this heuristic with a P-value of .015. In sum, it is highlyunlikely that several such tightly functionally linked groups would be present in a randomcollection of 21 genes. This is extremely strong evidence against the hypothesis that thesemutations became frequent through drift rather than natural selection."

I don't think the propsoed sources for natural selection here are very strong, but I'm at least ready to believe that some sort of selction was going on; adn much more excited about seeing the evidence for the effects of sphingolipids on brain growth and development. That seems to be the interesting stuff in all this!